Pathology of celiac disease: An insight about etiopathogenesis, pathophysiology and histologic diagnosis
Main Article Content
Abstract
Celiac disease (CD) is an immune mediated disorder characterized by intolerance to glutens in certain grains like wheat, barley, and rye. The gliadin exposure in susceptible individuals leads to an inflammatory reaction with damage to the small intestinal mucosa with villous blunting, atrophy and ultimate disappearance of intestinal villi. The damaged intestinal villi lead to malabsorption.
The development of celiac disease (CD) is determined by both environmental and genetic factors. The gluten in the grains represents an environmental factor. In addition to this environmental factor, CD development involves genetic predisposition as most CD patients possess human leucocyte antigen (HLA) DQ2 and/or HLA-DQ8. The complex interplay of multiple genetic and environmental factors determines the development of CD.
Small bowel mucosal biopsies remain gold standard for the diagnosis of CD because of variation in the clinical findings and serologic testing. Histologic examination of small intestine also helps to monitor the course of disease, response to treatment, and in detecting potential complications of celiac disease such as enteropathy associated T-cell lymphoma, adenocarcinoma, and concurrent intestinal diseases.
There has been significant development in understanding the pathophysiology, pathogenesis, and diagnosis of celiac disease. The present review summarizes the important development in CD in last few years with special emphasis on etiopathogenesis, pathophysiology, and pathologic features of CD. Better understanding of these features is not only important for correct diagnosis but also results in better patient management and would pave a way for future research of this overly complex disease characterized by complex interaction of environmental, genetic as well as immunologic mechanisms.
Keywords:
Celiac disease, Gluten intolerance, Small intestine biopsy, Villous atrophy, HLA-DQ2/HLA-DQ8, Malabsorption, Enteropathy-associated T-cell lymphoma, Pathophysiology of celiac disease
Article Details
How to Cite
TINGURIA, Mukund.
Pathology of celiac disease: An insight about etiopathogenesis, pathophysiology and histologic diagnosis.
Medical Research Archives, [S.l.], v. 12, n. 9, sep. 2024.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/5696>. Date accessed: 22 dec. 2024.
doi: https://doi.org/10.18103/mra.v12i9.5696.
Section
Review Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
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3. Tinguria M, Liaconis H. Cavitating mesenteric lymph node syndrome: A rare complication of celiac disease. A case report with clinicopathologic features and review of literature, Human Pathology Reports, Volume 26, 2021.
4. Shewry R, Tatham A, Kasarda D. Cereal proteins and coeliac disease. In: Marsh M, editor. Coeliac Disease. Oxford, UK: Blackwell Scientific Publications; 1992
5. Shewry P. What is gluten—why is it special? Front. Nutr. 2019, 6:101
6. Shan L, Molberg O, Parrot I, et al. Structural basis for gluten intolerance in celiac sprue. Science. 2002;297:2275–9.
7. Shan L, Qiao SW, Arentz-Hansen H, et al. Identification and analysis of multivalent proteolytically resistant peptides from gluten: implications for celiac sprue. J Proteome Res. 2005;4(5):1732–1741
8. Hemming-Harlo M, Lahdeaho M, Maki M. et al. Rotavirus vaccination does not increase type 1 diabetes and may decrease celiac disease in children and adolescents. Pediatr. Infect. Dis. J. 2019, 38:539– 41
9. Inns T, Fleming K, Iturriza-Gomara M. et al. Paediatric rotavirus vaccination, coeliac disease, and type 1 diabetes in children: a population-based cohort study. BMC Med. 2021, 19:147
10. Stordal K, Kahrs C, Tapia G. et al. Review article: exposure to microbes and risk of coeliac disease. Aliment Pharmacol Ther (2020) 53:43–62.
11. Nistico L, Fagnani C, Coto I, Percopo S, Cotichini R, et al. 2006. Concordance, disease progression, and heritability of coeliac disease in Italian twins. Gut 55:803–8
12. Kuja-Halkola R,Lebwohl B, Halfvarson J,Wijmenga C, Magnusson PK, Ludvigsson JF. 2016. Heritability of non-HLA genetics in coeliac disease: a population-based study in 107 000 twins. Gut 65:1793–98
13. Dube C, Rostom A, Sy R. et al. The prevalence of celiac disease in average-risk and at-risk Western European populations: a systematic review. Gastroenterology, 2005: 128:S57–S67
14. Sollid L, Markussen G, Ek J. et al. Evidence for a primary association of celiac disease to a particular HLA-DQ alpha/beta heterodimer. J Exp Med 169:345–350
15. Spurkland A, Ingvarsson G, Falk E. et al. Dermatitis herpetiformis and celiac disease are both primarily associated with the HLA-DQ (alpha 1*0501, beta1*02) or the HLA-DQ (alpha 1*03, beta 1*0302) heterodimers. Tissue Antigens, 1997 : 49 :29–34
16. Mearin M, Biemond I, Pena A. et al. HLA-DR phenotypes in Spanish coeliac children: their contribution to the understanding of the genetics of the disease. Gut, 1983: 24:532–537
17. Van de Wal Y, Kooy Y, Van V. et al. Selective deamidation by tissue transglutaminase strongly enhances gliadin-specific T cell reactivity. J Immunol, 1998a: 161:1585–1588
18. Hunt K, Zhernakova A, Turner G. et al. Newly identified genetic risk variants for celiac disease related to the immune response. Nat Genet, 2008: 40:395–402
19. Morbe U, Jorgensen P, Fenton T. et al. Human gut-associated lymphoid tissues (GALT); diversity, structure, and function. Mucosal Immunol. 2021: 14:793–802
20. Weisel N, Weisel F, Farber D. et al. Comprehensive analyses of B-cell compartments across the human body reveal novel subsets and a gut-resident memory phenotype. Blood, 2020: 136:2774–85
21. Bartolome-Casado R, Landsverk O, Chauhan S. et al. Resident memory CD8 T cells persist for years in human small intestine. J. Exp. Med. 2019: 216:2412–26
22. Bartolome-Casado R, Landsverk O, Chauhan S. et al. CD4+ T cells persist for years in the human small intestine and display a TH1 cytokine profile. Mucosal Immunol. 2021: 14:402–10
23. Landsverk O, Snir O, Casado R. et al. Antibody-secreting plasma cells persist for decades in human intestine. J. Exp. Med. 2017 : 214 :309–17
24. Mayassi T, Ladell K, Gudjonson H. et al. Chronic inflammation permanently reshapes tissue-resident immunity in celiac disease. Cell, 2019 : 176 :967–81. e19
25. Meresse B, Chen Z, Ciszewski C. et al. Coordinated induction by IL15 of a TCR-independent NKG2D signaling pathway converts CTL into lymphokine-activated killer cells in celiac disease. Immunity 2004: 21:357–66
26. Hüe S, Mention J, Monteiro R. et al. A direct role for NKG2D/MICA interaction in villous atrophy during celiac disease. Immunity 2004: 21:367–77
27. Halstensen T, Brandtzaeg P. Activated T lymphocytes in the celiac lesion: non-proliferative activation (CD25) of CD4+ α/β cells in the lamina propria but proliferation (Ki-67) of α/β and γ/δ cells in the epithelium. Eur. J. Immunol. 1993: 23:505–10
28. Dahal-Koirala S, Risnes L, Sollid L. Pathogenesis of coeliac disease—a disorder driven by gluten-specific CD4+ T cells. In Coeliac Disease and Gluten-Related Disorders, ed. A Schiepatti, DS Sanders, 2022, pp. 41–68. London: Academic Press
29. Baklien K, Brandtzaeg P, Fausa O. 1977. Immunoglobulins in jejunal mucosa and serum from patients with adult coeliac disease. Scand. J. Gastroenterol. 1977: 12:149–59
30. Pinto D, Montani E, Bolli M. et al. A functional BCR in human IgA and IgM plasma cells. Blood 2013: 121:4110–14
31. Di Niro R, Mesin L, Raki M. et al. Rapid generation of rotavirus specific human monoclonal antibodies from small-intestinal mucosa. J. Immunol. 2010: 185:5377–83
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